Antivirals that target the host IMPα/β1-virus interface

Area of Science:

• Virology
• Molecular Biology
• Drug Discovery

Background:

• Nuclear import mediated by importin (IMP) α/β1 is crucial for viral replication.
• Many viruses, including HIV-1, DENV, and ZIKV, rely on the IMPα/β1-virus interface for infection.
• Small molecule inhibitors targeting this interface have emerged as a promising antiviral strategy.

Purpose of the Study:

• To review the antiviral potential of targeting the IMPα/β1-virus interface.
• To highlight key small molecule inhibitors, ivermectin and 4-HPR.
• To discuss the clinical progress and therapeutic potential of these agents.

Main Methods:

• Review of existing literature on IMPα/β1-dependent nuclear import inhibitors.
• Analysis of high-throughput compound screening data.
• Summary of clinical trial outcomes and preliminary results for ivermectin and 4-HPR.

Main Results:

• Ivermectin, an FDA-approved drug, demonstrates broad-spectrum activity against numerous viruses (HIV-1, DENV, ZIKV, SARS-CoV-2).
• Phase III trials for Dengue and numerous trials for SARS-CoV-2 are ongoing, with preliminary data suggesting clinical benefit.
• N-(4-hydroxyphenyl) retinamide (4-HPR) specifically targets viral non-structural protein 5 (NS5) and inhibits DENV and ZIKV infections, with Phase II trials planned.

Conclusions:

• The IMPα/β1-virus interface represents a viable therapeutic target for broad-spectrum antiviral drug development.
• Ivermectin and 4-HPR show significant promise, supported by ongoing clinical investigations.
• Rigorous randomized clinical trials are essential to confirm the therapeutic efficacy of these IMPα/β1-targeting agents.